Echium Oil Modulates Macrophage Inflammation by Promoting Alternative Activation

蓝蓟油通过促进替代激活来调节巨噬细胞炎症

基本信息

批准号：
7743990
负责人：
Amanda Wibley
金额：
$ 3.58万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7743990
关键词：
A Mouse Acute Address Anti-Inflammatory Agents Anti-inflammatory Apoptotic Arachidonate 15-Lipoxygenase Arginine Atherogenic Diet Atherosclerosis Bacteriophages Binding Biological Assay Biological Models Bone Marrow Botanicals CD36 gene Cells Chronic Chronic Disease Conditioned Culture Media Consumption Data Diabetes Mellitus Diet Dinoprostone Docosahexaenoic Acid n-3 Echium Eicosapentaenoic Acid Enzymes Fatty Acids Fish Oils Fishes Flow Cytometry Food Gene Expression Genes Genetic Genomics Goals Greater sac of peritoneum Incidence Incubated Inflammation Inflammatory Inflammatory Response Injection of therapeutic agent Interleukin-10 Interleukin-4 Interleukin-6 Knockout Mice Leukotrienes Ligand Binding Ligands Ligation Linolenic Acids Linseed Oil Lipids Low Density Lipoprotein Receptor Macrophage Activation Mammals Measures Mediating Medicine Metabolism Modeling Modification Molecular Mus Nuclear Hormone Receptors Oils Omega-3 Fatty Acids Oxis PPAR gamma PTGS2 gene Pathogenesis Pathway interactions Peritoneal Peritoneal Macrophages Peroxisome Proliferator-Activated Receptors Persons Phagocytosis Phenotype Physiological Play Population Population Decreases Research Resolution Reverse Transcriptase Polymerase Chain Reaction Rheumatoid Arthritis Risk Role Seeds Severity of illness Small Interfering RNA Source Spleen Supplementation Surveys Symptoms Testing Thioglycolates Transactivation Transcriptional Activation Ubiquitin United States acquired immunity arginase base cell motility chromatin immunoprecipitation cytokine dietary supplements enzyme activity feeding in vivo lymph nodes macrophage mannose receptor mouse model novel palm oil protein inhibitor of activated STAT 1 response sensor stearidonic acid toll-like receptor 4 transcription factor ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): This proposal is focused on complementary and alternative approaches to medicine geared toward understanding the molecular mechanisms of macrophage activation. It addresses the possibility that omega-3 fatty acids, like those found in fish oil, modulate inflammation by promoting alternative activation. The nuclear hormone receptor PPAR gamma acts as a lipid-sensor and likely directs this modulation of macrophage activation phenotypes by omega-3 fatty acids. Furthermore, PPAR gamma is a well recognized transcription factor that has been shown to regulate several aspects of macrophage cellular metabolism. However, the regulatory roles of fatty acids in macrophage inflammation are poorly understood. The studies herein will help to further investigate cellularly, molecularly, and genetically, how fatty acids may alleviate chronic diseases symptoms. In specific aim 1 we will test the hypothesis that dietary enrichment with seed oil from Echium plantagineum has the ability to ameliorate inflammation similar to fish oil in a mouse model of atherosclerosis and chronic inflammation. This will serve as an in vivo approach to ask the question if supplementation with a botanical source of omega-3 fatty acids causes alternative activation in macrophages, as a means to reduce pro-inflammatory phenotypes and responses. In specific aim 2 we will use genomic, cell based and molecular approaches to address the role of PPAR gamma in the macrophage response to omega-3 fatty acids. We will systematically look at the coordinate roles of PPAR gamma transcriptional activation and inflammatory gene transrepression pathways in modulating omega-3 fatty acid responses. We also test the hypothesis that the shifting of macrophage phenotypes caused by omega-3 fatty acid enrichment is dependent on the enzymatic activity of 12/15-lipoxygenase, a lipid-peroxidizing enzyme. It is well established that 12/15-lipoxygenase produces fatty acid-derived ligands that may serve to activate PPAR gamma endogenously. The significance of this project is two-fold. First, it lies in the determination of whether echium oil, a botanical source of omega-3 fatty acids, possesses the anti-inflammatory potential offish oil. Secondly, it will provide novel mechanistic data on the role of n-3 PUFAs in ameliorating inflammaiton and whether this occurs through priming macrophages toward inflammationresolving, alternatively activated phenotypes, a field in which strong support is lacking. If our hypothesis is correct, the results will support the rationale for inclusion of stearidonic acid-enriched botanical oils, as from Echium plantagineum, in food products providing a source of n-3 PUFAs that could reduce inflammation in the population, and decrease the risk of atherosclerosis and other chronic diseases.

描述（由申请人提供）：该提案的重点是用于理解巨噬细胞激活的分子机制的互补和替代方法。它解决了omega-3脂肪酸与鱼油中的脂肪酸一样的可能性，可以通过促进替代激活来调节炎症。核激素受体PPAR伽玛充当脂质传感器，可能会通过omega-3脂肪酸来指导这种调节巨噬细胞激活表型。此外，PPAR伽马是一个公认的转录因子，已证明可以调节巨噬细胞的多个方面。但是，脂肪酸在巨噬细胞炎症中的调节作用知之甚少。本文的研究将有助于进一步研究细胞，分子和遗传学，脂肪酸如何减轻慢性疾病的症状。在特定目的1中，我们将测试以下假设：在动脉粥样硬化和慢性炎症的小鼠模型中，植物eChium plantagineum的种子油具有相似的炎症的能力。这将作为一种询问一个问题的体内方法，以补充欧米茄3脂肪酸的植物来源是否会在巨噬细胞中引起替代激活，以减少促炎性表型和反应。在特定的目标2中，我们将使用基因组，基于细胞和分子方法来解决PPAR伽马在巨噬细胞对Omega-3脂肪酸巨噬细胞反应中的作用。我们将系统地研究PPAR伽马转录激活和炎症基因变形途径在调节omega-3脂肪酸反应中的坐标作用。我们还检验了以下假设：由omega-3脂肪酸富集引起的巨噬细胞表型的转移取决于12/15-氟加氧酶的酶活性，一种脂质过氧化物酶。众所周知，12/15-脂氧合酶会产生脂肪酸衍生的配体，这些配体可能用于内源性地激活PPAR伽马。该项目的重要性是两个倍。首先，它在于确定欧米茄3脂肪酸的植物源是否具有抗炎电位脱油油。其次，它将提供有关N-3 PUFA在改善炎症的作用的新型机械数据，以及是否通过将巨噬细胞启动到炎症分辨，替代激活的表型而发生，这是缺乏强大支持的领域。如果我们的假设是正确的，结果将支持含有替代酸的植物油的基本原理，如来自plantagineum echium plantagineum的食品，提供N-3 PUFA的来源，可以减少人群中的炎症，并减少风险动脉粥样硬化和其他慢性疾病。